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Asthma I Notes

Pharmacology Notes > Drug Development (BIOL10822) Notes

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A chronic disease characterised by narrowing of the peripheral airways in the lung, varying in severity over short periods of time either spontaneously or in response to treatment.
Predominantly inflammatory.

- Asthma is a chronic disorder of the lungs, involving paroxysmal obstruction of the airways. It is characterised by being primarily reversible, although if untreated it can lead to irreversible changes in lung function.
- FEV1 is the volume of air that can be exhaled from the lungs in one second,
following a maximum inspiration.
- PEFR is the maximum flow rate developed by the lungs after a maximal inspiration.
- Both of these parameters are compromised in asthma and are frequently used to measure lung function.
- In the U.K.
à No. of persons afflicted > 5,000,000
à Annual no. of deaths from asthma < 1,200
à Annual cost to nation > £2,200m

A chronic disease characterised by narrowing of the peripheral airways in the lung. Poorly reversible. A combination of chronic bronchitis and emphysema. Predominantly inflammatory.

- COPD can produce similar symptoms to asthma and is treated similarly (though antiinflammatory drugs are generally not as effective as in asthma).
- It is primarily caused by smoking and exposure to environmental pollutants (though there are some genetic factors too).
- COPD differs from asthma in that it is a progressive and poorly reversible disorder. It affects around 1 million people in the UK and is the 6th leading cause of death.

- Genetic factors - Allergy and Atopy genes
- Environmental influences in early life (e.g. maternal smoking, intrauterine nutrition,
avoidance of dietary and environmental allergens in first few years of life)
The genetic factors, combined with early environmental factors, lead to an individual having a
"background tendency" to asthma. This can then be triggered by environmental factors later in life. SPECIFIC TRIGGERS:Excreta of house dust mites
Exercise or emotion
Cold air
Respiratory tract infections
Animal fur, dander, saliva
Fungal spores
Occupational factors
Drugs (e.g. aspirin)
Environmental pollutants

- However, these basically divide the disorder into allergic and non-allergic origins.
- One other form that you need to be aware of is status asthmaticus. This is a severe acute asthma attack that is not readily reversed. It is a medical emergency and if treatment is not administered promptly, can be fatal.

- The trachea and primary bronchi are surrounded by rings of cartilage that holds them patent. As we move down to the secondary and tertiary bronchi, there is progressively less cartilage -
it becomes plates to begin with and is absent by the time we get down to the bronchioles.
- The bronchioles, which terminate in the gas exchange surfaces (the alveoli) do not have cartilage support but have much more smooth muscle. The tone of this smooth muscle plays a major role in determining the diameter of the bronchioles and thus the flow of air to the alveoli. ASTHMA - PATHOLOGICAL CHANGES IN THE AIRWAY WALL:

- In the typical aireway there is a submucosal layer containing glands; smooth muscle and an epithelial layer with goblet cells (single celled mucous glands) and ciliated epithelium. The cilia beat in a coordinated fashion to help move dirt and mucus out of the lungs. These are absent from the alveoli.
- In the asthmatic airway dramatic changes have taken place. There are many more glands in the submucosal layer, more muscle, and the submucosa is infiltrated by cells of the immune system. There may also be oedema. The basement membrane becomes thicker and there is a loss of the epithelium (especially the ciliated cells -
the goblet cells may increase in number. Mucus plugs may also form.Here we have histological samples from a normal individual and someone who died of an asthma attack. This illustrates the same pathological changes

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